A Phase III Study of Datopotamab Deruxtecan With or Without Durvalumab Compared With Chemotherapy and Pembrolizumab in PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer
Led by AstraZeneca · Updated on 2026-04-30
625
Participants Needed
316
Research Sites
165 weeks
Total Duration
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Brief Title
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Sponsors
A
AstraZeneca
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating treatments for participants with PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) in this Phase III, randomized, open-label, international study. The study aims to compare the effectiveness and safety of Datopotamab Deruxtecan (Dato-DXd) combined with durvalumab against investigator's choice chemotherapy combined with pembrolizumab, and also evaluates Dato-DXd alone. The main goal is to assess whether Dato-DXd with durvalumab helps participants live longer without their cancer worsening or improves overall survival compared to the standard chemotherapy plus pembrolizumab.
Participants are assigned to one of three treatment groups: Dato-DXd combined with durvalumab; investigator's choice chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) combined with pembrolizumab; or Dato-DXd alone. All treatments are given by intravenous infusion. The study includes stratification by geographic location, disease-free interval history, and prior PD-1/PD-L1 treatment for early stage TNBC.
Throughout the study, participants will undergo regular assessments including imaging to measure cancer progression, laboratory tests, and evaluations of symptoms and quality of life. Researchers will monitor progression-free survival, overall survival, response rates, duration of response, and time to deterioration in symptoms such as pain and physical functioning. Safety and tolerability of the treatments will also be closely observed. Participation may last up to several years with ongoing follow-up to capture long-term outcomes.
CONDITIONS
Brief Title
A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
Adults with histologically or cytologically confirmed locally recurrent inoperable or metastatic triple-negative breast cancer
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
PD-L1 positive status with combined positive score of 10 or higher confirmed by a validated test
No prior chemotherapy or systemic treatment for metastatic or recurrent breast cancer
Measurable disease as per RECIST 1.1 criteria
Adequate bone marrow and organ function
Ability to provide tumor tissue sample collected within 3 years
Eligible for one of the chemotherapy options: paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin
Male and female participants of childbearing potential agree to use specified contraception methods
For patients with recurrent disease, at least 6 months must have passed since completion of prior curative treatment
You will not qualify if you...
Presence of severe or uncontrolled medical conditions including systemic diseases, uncontrolled hypertension, serious gastrointestinal issues, or substance abuse
History of another primary cancer within 2 years unless treated with curative intent and no active disease
Previous treated spinal cord compression or inactive brain metastases if recovered and not requiring corticosteroids or anticonvulsants
Uncontrolled infections requiring intravenous antibiotics, antivirals or antifungals
Active or uncontrolled hepatitis B or C virus infection
Known HIV infection not well controlled
Significant cardiac disease or pulmonary function compromise
History or current interstitial lung disease or pneumonitis requiring steroids
Clinically significant corneal disease
Active or prior autoimmune or inflammatory disorders
Prior exposure to treatments targeting topoisomerase I or TROP2 therapies
Concurrent anti-cancer treatments
Known severe allergy to PD-1/PD-L1 inhibitors or Dato-DXd
Current pregnancy, breastfeeding, or planning pregnancy
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 33 months or until disease progression or discontinuation
Participants receive treatment with either Dato-DXd with or without durvalumab, or investigator's choice of chemotherapy in combination with pembrolizumab, to assess effectiveness and safety in managing PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer.
Regular visits for treatment administration and monitoring as per protocol
Follow-up
Duration - Up to 31 months after treatment completion (up to 64 months total from randomization)
Participants are monitored for overall survival, subsequent therapies, and long-term safety after completing treatment.
Visits as scheduled for assessments and survival follow-up
TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer.
Peter Schmid, Mafalda Oliveira, Joyce O'Shaughnessy...